Thrombosis and meningococcal infection rates in pegcetacoplan-treated patients with paroxysmal nocturnal hemoglobinuria in the clinical trial and postmarketing settings.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis and thrombosis. Complement component 5 (C5) inhibitors have decreased PNH-related thrombosis rates and reduced mortality compared with those of age-matched controls. A small but significantly increased risk of life-threatening Neisseria infections, especially N meningitidis, represents a long-term safety risk of complement inhibition. Objectives: To evaluate the rates of thrombosis and meningococcal infections in patients with PNH treated with the complement component 3-targeted therapy pegcetacoplan. Methods: Cumulative patient-year exposure to pegcetacoplan was calculated, and thrombotic events and meningococcal infections were reviewed in 7 clinical trials and in the postmarketing setting. The clinical trial protocols and pegcetacoplan labeling required vaccination against Streptococcus pneumoniae, N meningitidis, and Haemophilus influenzae before pegcetacoplan use; the label allowed for prophylactic antibiotic use if pegcetacoplan must be administered before vaccination. Results: As of November 13, 2022, 464 patients with PNH had 619.4 patient-years of pegcetacoplan exposure in completed/ongoing clinical trials and the postmarketing setting. Seven thrombotic events were reported: 5 in clinical trials (2 in the same patient) and 2 in the postmarketing setting. The overall thrombosis rate was 1.13 events per 100 patient-years (clinical trials: 1.22 events/100 patient-years in 409.4 years; postmarketing: 0.95 events/100 patient-years in 210.0 years). No infections with meningococcal bacteria were reported. Conclusion: Event rates for thrombosis were comparable between pegcetacoplan and previously reported rates of C5 inhibitors in patients with PNH, and no cases of meningococcal infection were reported with pegcetacoplan. Continued follow-up is required.

Analyzing the dynamics of meningococcal vaccinations initiatives by local government units in Poland (2017-2021) - Scope, challenges and recommendations.

INTRODUCTION: Meningococcal vaccinations are recommended by Polish public health authorities but lack coverage under health insurance, prompting Local Government Units (LGUs) to implement local health policy programs. This study examines the effectiveness and impact of LGU-driven meningococcal vaccination initiatives in Poland between 2017 and 2021. MATERIAL AND METHODS: A retrospective analysis utilized data from reports on local public health interventions submitted annually to the Ministry of Health in Poland. The study focused on the number of meningococcal vaccination programs, their scope, the vaccinated population, and associated program costs. Additionally, nationwide data on meningococcal disease incidence and vaccine uptake were analyzed. RESULTS: Within LGUs programs, 48,617 individuals received meningococcal vaccinations, constituting approximately 10% of all vaccinations in Poland during the study period. Notably, cities with poviat rights spearheaded programs covering 54% of the total participants. The total cost incurred by these initiatives amounted to EUR 2,553,661. CONCLUSIONS: While LGUs activities positively contributed to increased meningococcal vaccination rates, the overall engagement of local governments remains limited. The findings underscore the importance of expanding local government involvement in meningococcal vaccination programs to address public health needs effectively. Improved collaboration and increased funding may enhance the reach and impact of these initiatives.

Serogroup B Invasive Meningococcal Disease in Older Adults Identified by Genomic Surveillance, England, 2022-2023.

We report a cluster of serogroup B invasive meningococcal disease identified via genomic surveillance in older adults in England and describe the public health responses. Genomic surveillance is critical for supporting public health investigations and detecting the growing threat of serogroup B Neisseria meningitidis infections in older adults.

Epidemiology of Invasive Meningococcal Disease in Colombia: A Retrospective Surveillance Database Analysis.

INTRODUCTION: Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, is associated with high morbidity and mortality. The aim of the current study was to describe the historical and recent epidemiology of IMD in Colombia. METHODS: This retrospective surveillance database analysis examined all available data on IMD in Colombia. Data were extracted from publicly available disease event reports and laboratory surveillance reports or obtained directly from hospitals in Cartagena. RESULTS: During 2015-2021, the overall incidence of IMD was 0.04-0.18 per 100,000 based on laboratory surveillance reports. IMD incidence was highest among infants aged < 1 year (0.52-1.47 per 100,000), as was IMD mortality (0.00-0.65 per 100,000). Serogroup B was the dominant serogroup responsible for IMD in Colombia during 1988-2014, but, since 2015, serogroup C has been dominant in all age groups, followed by serogroups B and Y. During 2010-2021 combined, the majority of IMD cases were reported in Bogotá (31.9%) and Antioquia (21.7%). Of 42 IMD cases in the city of Cartagena, 54.8% occurred in people who lived in the poorest neighborhoods, and these patients had the highest IMD lethality (52.2%) and the shortest median hospitalization duration (3 days). CONCLUSION: The overall incidence of IMD in Colombia was low but was highest among infants aged < 1 year. IMD cases tended to be concentrated in the more densely populated areas and in poorer neighborhoods. As the majority of IMD cases in Colombia since 2015 have been serogroup C, followed by B or Y, vaccination to protect against these serogroups could potentially be beneficial and help to achieve the World Health Organization's and Pan American Health Organization's roadmaps to defeat meningitis by 2030.

Accuracy of antigen tests for meningococcal meningitis in cerebrospinal fluid: A diagnostic meta-analysis.

OBJECTIVES: Neisseria meningitidis is one of the major pathogens of meningitis in children worldwide and causes invasive meningococcal disease (IMD), which is a critical illness that mainly presents as meningitis and/or septicemia in children. Identification of N. meningitidis in cerebrospinal fluid (CSF) is the gold standard for the diagnosis of meningococcal meningitis, but antigen tests have advantages such as timely results, relatively low cost, and convenience. Yet, the diagnostic accuracy of antigen tests remains uncertain. Therefore, the aim of this meta-analysis was to evaluate the diagnostic accuracy of antigen tests for N. meningitidis in CSF. METHODS: We searched the PubMed, Embase, and Cochrane Library databases for studies evaluating the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We included studies that provided sufficient data to construct a 2 × 2 table on a per-sample basis. To determine the overall sensitivity and specificity of the antigen tests, we used polymerase chain reaction (PCR) as the reference standard and employed the hierarchical summary receiver operating characteristic model. RESULTS: Nine studies with 4533 CSF samples were included. The meta-analysis yielded a pooled sensitivity of 91.2% (95% confidence interval [CI]: 80.0%-100.0%) and a pooled specificity of 93.8% (95% CI: 83.9%-100.0%). A subgroup analysis of 2 studies that reported the outcomes of MeningoSpeed yielded a pooled sensitivity of 93.4% (95% CI: 90.0%-95.8%) and a pooled specificity of 91.9% (95% CI: 88.6%-94.4%). Antigen testing for the N. meningitidis serogroup X had a pooled sensitivity of 92.4% (95% CI: 85.2%-96.2%) and a pooled specificity of 99.2% (95% CI: 78.7%-100.0%). CONCLUSIONS: The studied antigen tests had high sensitivity and specificity for the diagnosis of meningococcal meningitis in CSF specimens. Antigen testing could serve as an accurate diagnostic method for assessing patients who have a suspected N. meningitidis infection.

Epidemiology of invasive meningococcal disease and its sequelae: a population-based study in Italian primary care, 2000-2019.

BACKGROUND: Invasive meningococcal disease (IMD) is a severe infectious disease. Although effective preventive and therapeutical strategies are available, the fatality rate remains high in the general population, with an occurrence of meningococcal-related severe sequelae involving 10-20% of survivors. Given the crucial role of general practitioners in recognizing and preventing IMD and its related sequelae, we aim to assess the burden of these conditions in primary care. METHODS: Using an Italian primary care database, the incidence rate of IMD was calculated in the period 2000-2019 by capturing the first diagnosis registered during follow-up. As far as meningococcal-related sequelae are concerned, we identified and clinically evaluated each potential sequela during the first 3 months, from 3 to 12 months, and up to 36 months. RESULTS: Among 508 patients diagnosed with IMD, 403 (incidence rate: 0.24 per 10,000 person-years) comprised those diagnosed with IMD in patients aged 15 years or older. We ascertained 104 sequelae (20.4%); 76% of them occurred in those aged 25 or older; 42, 27, and 35 were assessed as short-, medium-, or long-term sequelae, respectively. Overall, 4.7% of IMD patients reported physical sequelae, while 12.2% and 5.7% of patients reported neurological and psychological sequelae, respectively. CONCLUSION: Our study showed that a substantial proportion of IMD and related sequelae occur in individuals aged over 25, with a non-negligible burden for healthcare systems. As for the paediatric population, effective communication on the relevance of meningococcal vaccination in adults should be proficiently fostered.

Serum bactericidal activity against circulating and reference strains of meningococcal serogroup B in the United States: A review of the strain coverage of meningococcal serogroup B (MenB) vaccines in adolescents and young adults.

Invasive meningococcal disease (IMD) is rare but associated with high morbidity and mortality. In the United States, the most vulnerable age groups are infants and adolescents/young adults, and the most common type of IMD is caused by serogroup B (MenB). MenB is preventable among adolescents and young adults with the use of two licensed vaccines, MenB-FHbp (Trumenba®, bivalent rLP2086; Pfizer Inc, Collegeville, PA) and MenB-4C (Bexsero®; GSK Vaccines, Srl, Italy). Because the effectiveness of MenB vaccination is dependent on broad vaccine coverage across circulating disease-causing strains, we reviewed the available clinical and real-world evidence regarding breadth of coverage of the two licensed vaccines in adolescents and young adults in the United States. Both vaccines protect against various MenB strains. More controlled data regarding breadth of coverage across MenB strains are available for MenB-FHbp compared with MenB-4C, whereas more observational data regarding US outbreak strain susceptibility are available for MenB-4C.

Exploiting Real-Time Genomic Surveillance Data To Assess 4CMenB Meningococcal Vaccine Performance in Scotland, 2015 to 2022.

The United Kingdom implemented the first national infant immunization schedule for the meningococcal vaccine 4CMenB (Bexsero) in September 2015, targeting serogroup B invasive meningococcal disease (IMD). Bexsero contains four variable subcapsular proteins, and postimplementation IMD surveillance was necessary, as nonhomologous protein variants can evade Bexsero-elicited protection. We investigated postimplementation IMD cases reported in Scotland from 1 September 2015 to 30 June 2022. Patient demographics and vaccination status were combined with genotypic data from the causative meningococci, which were used to assess vaccine coverage with the meningococcal deduced vaccine antigen reactivity (MenDeVAR) index. Eighty-two serogroup B IMD cases occurred in children >5 years of age, 48 (58.5%) of which were in unvaccinated children and 34 (41%) of which were in children who had received ≥1 Bexsero dose. Fifteen of the 34 vaccinated children had received one dose, 17 had received two doses, and two had received three doses. For 39 cases, meningococcal sequence data were available, enabling MenDeVAR index deductions of vaccine-preventable (M-VP) and non-vaccine-preventable (M-NVP) meningococci. Notably, none of the 19 of the children immunized ≥2 times had IMD caused by M-VP meningococci, with 2 cases of NVP meningococci, and no deduction possible for 17. Among the 15 children partially vaccinated according to schedule (1 dose), 7 were infected by M-VP meningococci and 2 with M-NVP meningococci, with 6 for which deductions were not possible. Of the unvaccinated children with IMD, 40/48 were ineligible for vaccination and 20/48 had IMD caused by M-VP meningococci, with deductions not being possible for 14 meningococci. IMPORTANCE This study demonstrates the value of postimplementation genomic surveillance of vaccine-preventable pathogens in providing information on real-world vaccine performance. The data are consistent with 2 and 3 doses of Bexsero, delivered according to schedule, providing good protection against invasive disease caused by meningococci deduced from genomic data to be vaccine preventable. Single doses provide poorer protection to infants. In practical terms, these data can provide public health reassurance when vaccinated individuals develop IMD with non-vaccine-preventable variants. They further indicate that additional testing is needed on variants for which no immunological data exist to improve estimates of protection, although these data suggest that the uncharacterized variants are unlikely to be covered by Bexsero. Finally, the confirmation that incomplete or absent doses in infancy lead to reduced protection supports public health and general practitioners in promoting vaccination according to schedule.

Epidemiología de la enfermedad meningocócica en República Dominicana 2012-2022: bases para su prevención / Epidemiology of meningococcal disease in Dominican Republic 2012-2022: strategies for its prevention

Objetivo: La Enfermedad Meningocócica Invasiva es una causa frecuente de morbimortalidad mundial. El objetivo de este estudioes describir la epidemiología de la enfermedad meningocócica en República Dominicana desde 2012 a 2022 y proponer las basespara su prevención.Método: En el análisis se calcularon incidencias, tasas de hospitalización por cada 100.000 habitantes, tasas de letalidad y se hizouna comparación entre grupos de edad de los 325 casos de meningococcemia reportados en el Sistema Nacional de VigilanciaEpidemiológica Dominicano durante estos 10 años.Resultados principales: El 33% de los casos (103) tenía menos de 5 años. Este grupo de edad fue el que tuvo la tasa de hospitalizaciónmás alta, la mayor tasa de mortalidad en edad pediátrica la mayor letalidad.Conclusiones: Si la República Dominicana vacunara a su población, debería comenzar con los menores de 5 años, y así se reduciríanlas hospitalizaciones, muertes, complicaciones y secuelas producidas por el meningococo. (AU)

Objective: Invasive meningococcal disease is a frequent cause of morbidity and mortality worldwide. The aim of this study is todescribe the epidemiology of meningococcal disease in the Dominican Republic from 2012 to 2022 and to propose the basis for itsprevention.Methods: Incidences, hospitalization rates per 100,000 population, case fatality rates and a comparison between age groups ofthe 325 cases of meningococcemia reported in the Dominican National Epidemiological Surveillance System during these 10 yearswere calculated in the analysis.Main results: 33% of the cases (103) were less than 5 years old. This age group had the highest hospitalization rate, the highestmortality rate in pediatric age and the highest case fatality rate.Conclusions: If the Dominican Republic were to vaccinate its population, it should start with those under 5 years of age, and thiswould reduce hospitalizations, deaths, complications and sequelae caused by meningococcus. (AU)

Momificación natural de falanges como consecuencia de meningococemia fulminante. A propósito de un caso / Natural mummification of phalanges as a consequence of fulminant meningococcemia. About a case

Fundamento: Las infecciones del sistema nervioso central constituyen una importante causa de morbilidad y mortalidad neurológica. La púrpura fulminante o meningococemia es una enfermedad grave que evoluciona a severas complicaciones y secuelas, sin embargo, es infrecuente que ocurra momificación o amputación natural de los dedos de las manos y los pies. Objetivo: Describir el caso de un paciente con meningococemia fulminante, al cual se le momificaron de manera natural las falanges de las manos y los pies como consecuencia de la enfermedad. Presentación del caso: Se presenta un paciente de 18 años de edad que fue diagnosticado con meningococemia. Clínicamente presentó fiebre, cefalea intensa, lesiones purpúrico hemorrágicas, petequias y hematomas en piel, evolutivamente shock séptico y disfunción múltiple de órganos. Posterior a 16 días de estadía en sala egresó vivo del hospital, pero con secuelas caracterizadas por momificación de las falanges de las manos y los pies. Conclusiones: La meningococemia es una enfermedad aguda, potencialmente mortal y se reporta mayormente en la edad pediátrica. Entre los sobrevivientes es infrecuente que ocurra la momificación de las falanges de las manos y los pies, como ocurrió en el caso reportado.

Background: Infections of the central nervous system are a significant cause of neurological morbidity and mortality. Purpura fulminans or meningococcemia is a serious disease that evolves into severe complications and sequelae, however it is infrequent for mummification or natural amputation of fingers and toes to occur. Objective: To describe the case of a patient with fulminant meningococcemia, in whom hands and feet phalanges were naturally mummified as a consequence of the disease. Case report: An 18-year-old patient diagnosed with meningococcemia is presented. Clinically, he presented fever, intense headache, purpuric hemorrhagic lesions, petechiae and bruises on the skin, progressively septic shock and multiple organ dysfunction. After 16 days in hospital, he was discharged alive, but with some sequelae characterized by mummification of the hands and feet phalanges. Conclusions: Meningococcemia is an acute, life-threatening disease and is mostly reported in the pediatric age. Mummification of the hands and feet phalanges is uncommon among survivors, as occurred in the reported case.

A policy review of the introduction of the MenACWY vaccine in toddlers across multiple countries.

INTRODUCTION: Immunization is the best strategy to protect individuals from invasive meningococcal disease (IMD). To support decision-making around immunization, this paper considers what has led four countries and regions of two more to introduce the quadrivalent MenACWY vaccine in toddlers (ages 12-24 months). AREAS COVERED: A narrative literature review was conducted to identify countries that have introduced a MenACWY vaccination program for toddlers. Information from peer-reviewed publications, reports, and policy documents for each identified country was extracted. Australia, Chile, the Netherlands, Switzerland, and regions of Italy and Spain have introduced the MenACWY vaccine in their toddler programs, driven by the rising incidence of MenW and MenY and the vaccine's ability to provide protection against other serogroups. Australia and the Netherlands considered the economic impacts of implementing a MenACWY toddler vaccination program. Vaccination uptake and effects are reported for three countries; however, in two, isolating the vaccine's effect from the collateral effect of COVID-related measures is difficult. EXPERT OPINION: Increased convergence of vaccination policies and programs is needed internationally, as IMD recognizes no borders.PL AIN LANGUAGE SUMMARYVaccination is the best defense against meningitis, a deadly disease. While someone of any age can contract it, children 0-24 months of age are disproportionately affected. The increasing number of cases of meningitis has led four countries plus regions of two more to introduce into their vaccination schedules for toddlers (ages 12-24 months) a vaccine that protects against four different serogroups rather than one serogroup alone. This paper considers what has driven that shift.

Risk Analysis by Age on the Burden of Meningococcal Disease in Spain.

We conducted an age-based risk analysis of meningococcal disease in Spain to provide prospects on a rational vaccine schedule in pediatrics. We used the National Hospital Registry to estimate meningococcal hospitalization rate. Population census for each year was used as the denominator in computing the hospitalization rate. We computed the odds ratio of each age using <1 year old as a reference group. From 1998 to 2017, 13,554 hospitalized cases were diagnosed, with a declining trend across the years. Infants (<1 year, n = 2425) and children (1−14 years, n = 6053) comprised the majority of all hospitalized meningococcal disease in Spain (62.5% or 8474/13,554). The incidence of hospitalization decreased dramatically with age from 56.2/100,000 in <1-year-old children to 1.3/100,000 in >5-year-old children. There was a dramatic decline in risk in 1 year (OR 0.58) to 4 years of age (OR 0.21). The risk continued to decline until 13 years old. Afterward, it had a minimal upward trajectory observed at 14−17 years old (OR 0.08). Infants and adolescents are at continued risk of invasive meningococcal disease in Spain. The highest risk occurs in infants. Surveillance data, together with evidence on long-term immunogenicity and capacity for herd effect, should be considered for a more relevant immunization schedule.

Risk Factors for Contracting Invasive Meningococcal Disease and Related Mortality: A Systematic Literature Review and Meta-analysis.

OBJECTIVES: To describe risk factors (RFs) and quantify their effects in invasive meningococcal disease (IMD) and associated mortality across all age groups based on the available published literature. METHODS: A systematic literature review (SLR) was conducted via MEDLINE® and Embase. Study selection, data extraction, and quality assessment were performed by two independent reviewers. Associations between RFs and outcomes were quantified via a meta-analysis (MA). RESULTS: Seventy-four studies (date range 1950 - 2018) were included in the SLR. Statistically significant RFs for contracting IMD identified from the SLR (within-study) included previous IMD infection and young age (0 - 4 years). MA indicated that significant RFs for contracting IMD (11 studies) were: HIV-positive status, passive smoke exposure, and crowded living space. In the MA for IMD-related mortality risk (11 studies), age 25 - 45 years (vs. 0 - 5 years) and serogroup C (vs. serogroup B) were significantly associated with increased risk. CONCLUSIONS: Previous findings of higher risk for IMD contraction with smoke exposure and crowded living conditions in children/adolescents have been extended by this SLR/MA to all age groups. We provide strong evidence for higher risk of IMD in HIV-positive individuals, and confirm previous findings of higher IMD-related mortality risk in adults aged 25 - 45.

Evaluating the Impact of Meningococcal Vaccines With Synthetic Controls.

Invasive meningococcal disease (IMD) has a low and unpredictable incidence, presenting challenges for real-world evaluations of meningococcal vaccines. Traditionally, meningococcal vaccine impact is evaluated by predicting counterfactuals from pre-immunization IMD incidences, possibly controlling for IMD in unvaccinated age groups, but the selection of controls can influence results. We retrospectively applied a synthetic control (SC) method, previously used for pneumococcal disease, to data from 2 programs for immunization of infants against serogroups B and C IMD in England and Brazil. Time series of infectious/noninfectious diseases in infants and IMD cases in older unvaccinated age groups were used as candidate controls, automatically combined in a SC through Bayesian variable selection. SC closely predicted IMD in absence of vaccination, adjusting for nontrivial changes in IMD incidence. Vaccine impact estimates were in line with previous assessments. IMD cases in unvaccinated age groups were the most frequent SC-selected controls. Similar results were obtained when excluding IMD from control sets and using other diseases only, particularly respiratory diseases and measles. Using non-IMD controls may be important where there are herd immunity effects. SC is a robust and flexible method that addresses uncertainty introduced when equally plausible controls exhibit different post-immunization behaviors, allowing objective comparisons of IMD programs between countries.

Caracterización de la meningoencefalitis bacteriana en la provincia Camagüey en el período de 2016-2020

Introducción: Las infecciones del sistema nervioso central constituyen un importante problema de salud en todas las regiones del planeta; representan un reto para el médico de asistencia, el microbiólogo y el epidemiólogo, en función de un precoz y correcto diagnóstico, elementos básicos para un pronóstico satisfactorio. Objetivo: Determinar el comportamiento de la meningoencefalitis bacteriana en la provincia Camagüey. Métodos: Se realizó un estudio observacional descriptivo, transversal y retrospectivo, sobre el comportamiento de la meningoencefalitis bacteriana en la provincia Camagüey en el periodo comprendido desde el 2016 hasta el 2020. El universo de estudio estuvo constituido por todos los casos (128) diagnosticados con meningoencefalitis bacteriana, atendidos en los hospitales de más de 100 camas durante el período del primero de enero de 2016 al 31 de diciembre de 2020. Resultados: El año 2017 resultó ser el mayor número de casos, el agente causal predominante fue el Streptococcus pneumoniae; las edades pediátricas fueron las de mayor incidencia en especial el menor de un año y sexo masculino. El síntoma cardinal en el estudio fue la fiebre y el neumococo fue el más letal agente causal. Conclusiones: El diagnóstico precoz de las meningoencefalitis bacterianas conlleva a una menor letalidad y por ende menos secuelas.

Introduction: Central nervous system infections are an important health problem in all regions of the planet; they represent a challenge for the attending physician, the microbiologist and the epidemiologist, based on an early and correct diagnosis, basic elements for a satisfactory prognosis. Objective: To determine the behavior of bacterial meningoencephalitis in the Province of Camagüey. Methods: A descriptive, cross-sectional and retrospective observational study was carried out on the behavior of bacterial meningoencephalitis in Camagüey province during the period 2016-2020. The study universe consisted of all cases (128) diagnosed with bacterial meningoencephalitis, attended in Hospitals with more than 100 beds during the period from January 1st, 2016 to December 31st, 2020. Results: The year 2017 turned out to be the one with the largest number of cases, the predominant causal agent was Streptococcus pneumoniae; pediatric ages were those with the highest incidence, especially those under 1 year of age and males. The cardinal symptom in the study was fever, and pneumococcus was the most lethal causative agent. Conclusions: The early diagnosis of bacterial meningoencephalitis leads to less lethality and therefore fewer sequelae.

Primary meningococcal arthritis of the hip due to serogroup W in a pediatric patient.

BACKGROUND: Primary meningococcal arthritis (PMA) is defined as the presence of acute septic arthritis with the identification of Neisseria meningitidis in synovial fluid or blood cultures but no clinical evidence of sepsis or meningitis. This report aimed to describe a clinical case of PMA caused by serogroup W, an uncommon etiology of this disease in Uruguay, and review the available literature. CASE REPORT: We report the case of a 5-year-old female, with no past medical history, admitted to the emergency department with a 12-hour history of fever of 39 °C and a limp. The patient was hemodynamically stable and had no clinical evidence of meningitis. Hip ultrasound showed an increase in synovial fluid. Arthrocentesis showed purulent exudate and synovial fluid culture showed no growth after five days. The blood culture showed isolates of N. meningitidis, serogroup W. The patient received treatment with ceftriaxone, and drainage of the affected joint was performed with excellent clinical response. CONCLUSIONS: Primary meningococcal arthritis is a rare presentation of meningococcal disease. Systematic arthrocentesis and the adequacy of antibiotic therapy when septic arthritis is clinically suspected are essential for confirming the diagnosis and decompressive drainage of the involved joint. This report is the first of PMA caused by serogroup W in Uruguay. Although the most common serogroup involved in meningococcal arthritis is serogroup B in Uruguay, an increase in serogroup W-related diseases has been reported in Chile and Argentina, emphasizing the need for epidemiological surveillance.

Carga y profilaxis de la enfermedad meningocócica invasiva: actualización sobre la vacunación frente al serogrupo B / Invasive meningococcal disease burden and prophylaxis: update on serogroup B vaccination

La enfermedad meningocócica invasiva (EMI) es una infección bacteriana grave que suele presentarsecomo meningitis o sepsis. Se transmite por las secreciones de nariz y boca, cursa con síntomas de evolución rápida que, si no se tratan, causan la muerte en 24-48 horas y puede acarrear secuelas devastadoras,como amputación de miembros, convulsiones, ictus y deterioro de la visión, habla y audición. El serogrupo(Men) B es el patógeno responsable de la mayoría de las EMI en Europa, América y Australia.La Organización Mundial de la Salud considera que la vacunación es el método más efectivopara combatir la meningitis meningocócica. Hasta la fecha no existe ninguna vacuna que protejade manera conjunta frente a todos los serogrupos causantes de EMI. Las vacunas de polisacáridosconjugados frente a MenACWY se han utilizado durante años, mientras que las dos vacunas frente aMenB han sido desarrollas recientemente. La vacuna MenACWY está incluida en el programa nacionalde inmunización español para adolescentes de 12 años. La Asociación Española de Pediatría proponeincluir también la vacuna MenB de manera sistemática para lactantes, ya que es el serogrupo másprevalente en España. Los farmacéuticos cumplen, como agentes sanitarios, una misión cotidianaesencial de asesoramiento y dispensación en las farmacias. Esta revisión ofrece información a losfarmacéuticos para ayudarles a resolver preguntas sobre la EMI, así como de su profilaxis con vacunasy así, puedan explicar a los padres la importancia de administrar las dosis de recuerdo para completarla pauta de vacunación. (AU)

Invasive meningococcal disease (IMD) is a serious bacterial infection commonly presenting as meningitisor sepsis. Transmitted through the mouth and nose secretions, it has rapidly evolving symptoms thatcan cause death in 24-48 hours if untreated and may also have devastating consequences, such as lossof limbs, seizures, stroke, as well as impairment of vision, speech, and hearing. Serogroup (Men) B is thepathogen responsible for most of cases of IMD in Europe, America, and Australia. The World Health Organization considers that vaccination is the most effective approach to defeatmeningococcal meningitis. For now, there is no single vaccine that protects against all serogroupscausing IMD. Conjugate polysaccharide vaccines against MenACWY have been available for years, andonly recently two MenB vaccines have been developed. MenACWY vaccination for adolescents aged12 years is included in the Spanish National Immunization Program and the Spanish Association ofPaediatrics suggests the systematic inclusion of the MenB vaccine as well for infants, as it is the mostprevalent serogroup in Spain. Pharmacists play an essential role as healthcare agents, advising anddispensing every day to patients who visit the pharmacy. This review provides information that willhelp pharmacists to answer questions relevant to IMD and prophylaxis with the available vaccines,so that they can explain to parents the importance of booster doses and vaccination schedulecompletion. (AU)

Eculizumab-Associated Moraxella lacunata Bacteremia and Systemic Inflammatory Response Syndrome in a Toddler with Atypical Hemolytic Uremic Syndrome.

Moraxella lacunata, a low-virulence Gram-negative coccobacillus, is classically associated with conjunctivitis and upper respiratory tract infections; systemic infections such as sepsis have rarely been reported, especially in children. We describe a 28-month-old girl with atypical hemolytic uremic syndrome and stage II chronic kidney disease on long-term eculizumab therapy who presented with systemic inflammatory response syndrome and was found to have Moraxella lacunata bloodstream infection. Eculizumab, a humanized monoclonal anti-C5 antibody, has been associated with susceptibility to infections with encapsulated bacteria, especially Neisseria meningitidis. This is the first report of an invasive bacterial infection with Moraxella lacunata in a pediatric eculizumab recipient.

Tobacco smoking and meningococcal disease in adolescents and young adults: a systematic review and meta-analysis.

OBJECTIVES: Systematically review the evidence on the association between active and passive tobacco smoking and invasive meningococcal disease (IMD) in adolescents and young adults aged 15-to-24-years. METHODS: Electronic searches were conducted in Ovid MEDLINE, EMBASE, and Web of Science to June 2020. Reference lists were hand-searched. Two independent reviewers screened articles for eligibility. Risk of bias was assessed using an adapted Risk of Bias in Non-Randomised Studies - of Interventions tool. Meta-analyses were conducted using random-effects models. RESULTS: Of 312 records identified, 13 studies were included. Five studies provided data on the association between active smoking and IMD in the target age group; pooled odds ratio (OR): 1.45 (95% CI: 0.93-2.26). The overall OR, including eight studies with a wider participant age range, was 1.45 (95% CI: 1.12-1.88). For passive smoking, the equivalent ORs were 1.56 (95% CI: 1.09-2.25) and 1.30 (95% CI: 1.06-1.59) respectively. All studies were at high risk of bias. CONCLUSIONS: Active and passive smoking may be associated with IMD in adolescents and young adults. Since active smoking has also been linked to meningococcal carriage, and passive smoking to IMD in young children, smoking cessation should be encouraged to reduce transmission and IMD risk in all ages.

Post-Marketing Surveillance Observational Study of Quadrivalent Meningococcal Diphtheria Toxoid Conjugate Vaccine (MenACWY-DT, MCV4/Menactra®) in the Republic of Korea, 2014-2019.

BACKGROUND: Invasive meningococcal disease is a notifiable disease in the Republic of Korea. The meningococcal (groups A, C, Y, and W) polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-DT, Menactra®) was licensed in the Republic of Korea in 2014. This post-marketing surveillance (PMS) observational study aims to assess the safety of MenACWY-DT administration of routine clinical care to individuals aged 9-23 months as a two-dose series at least 3 months apart and to individuals 2-55 years as a single dose. METHODS: The PMS observational study (NCT02864927) included participants aged 9 months to 55 years and who were given MenACWY-DT during routine healthcare visits. The study participants were followed-up for up to 30 days following vaccination (additional time was allowed for the visit or phone call to be conducted). Study outcomes included solicited and unsolicited adverse reactions, unexpected adverse events, and serious adverse events (SAEs). RESULTS: A total of 640 participants 9-23 months of age and 671 participants 2-55 years of age were eligible for safety analysis. Overall, AEs were reported by 35.3% of participants aged < 2 years and 45% of participants aged 2-55 years. Solicited adverse reactions were reported by 21.4% and 17.4% of participants aged < 2 years and 2-55 years, respectively. Unsolicited adverse reactions were reported by 26.1% and 37.9%, respectively. No vaccine-related SAEs occurred during the study. The AEs reported in Korean population were consistent with the known safety profile of MenACWY-DT, and most were of grade 1-2 in severity. CONCLUSIONS: This study did not detect any unanticipated or new safety findings of concern with MenACWY-DT in either of the study age groups, and provides reassurance that MenACWY-DT can be used as part of routine immunization care for the prevention of invasive meningococcal disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT02864927.